Weizman R, Leschiner S, Schlegel W, Gavish M
Tel Aviv Community Mental Health Center, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Brain Res. 1997 Oct 24;772(1-2):203-8. doi: 10.1016/s0006-8993(97)00815-9.
The peripheral-type benzodiazepine receptors (PBR) are involved in various cellular functions, including steroidogenesis. The impact of these receptor ligands has been demonstrated mainly in steroidogenic cells. The aim of the present study was to assess in intact female rats the effect of chronic (21 days) administration of the PBR ligands PK 11195 (15 mg/kg) and Ro 5-4864 (5 mg/kg), the mixed ligand diazepam (5 mg/kg), and the central benzodiazepine receptor ligand clonazepam (1 mg/kg) on PBR binding characteristics in steroidogenic (ovary and adrenal) and non-steroidogenic (uterus and kidney) organs, as well as on serum hormonal steroids (estradiol, progesterone, and corticosterone). Selective and mixed PBR ligands up-regulated PBR density in the two steroidogenic organs, while Ro 5-4864 also induced elevation of the receptor density in the non-steroidogenic organs. In contrast to Ro 5-4864, PK 11195 treatment down-regulated renal PBR. Clonazepam elevated adrenal PBR. On the serum hormonal level, Ro 5-4864 suppressed estradiol secretion. The other ligands did not affect hormonal steroid levels. It appears that in female rats, at least at these doses and dosing schedules, there is no correlation between the impact of chronic in vivo exposure to these agents on PBR density and ovarian and adrenal hormone levels.
外周型苯二氮䓬受体（PBR）参与多种细胞功能，包括类固醇生成。这些受体配体的作用主要在类固醇生成细胞中得到证实。本研究的目的是评估在完整雌性大鼠中，慢性（21天）给予PBR配体PK 11195（15毫克/千克）和Ro 5-4864（5毫克/千克）、混合配体地西泮（5毫克/千克）以及中枢苯二氮䓬受体配体氯硝西泮（1毫克/千克）对类固醇生成器官（卵巢和肾上腺）和非类固醇生成器官（子宫和肾脏）中PBR结合特性的影响，以及对血清激素类固醇（雌二醇、孕酮和皮质酮）的影响。选择性和混合性PBR配体上调了两个类固醇生成器官中的PBR密度，而Ro 5-4864也诱导了非类固醇生成器官中受体密度的升高。与Ro 5-4864相反，PK 11195处理下调了肾脏PBR。氯硝西泮提高了肾上腺PBR。在血清激素水平上，Ro 5-4864抑制了雌二醇分泌。其他配体未影响激素类固醇水平。看来在雌性大鼠中，至少在这些剂量和给药方案下，体内长期暴露于这些药物对PBR密度的影响与卵巢和肾上腺激素水平之间没有相关性。
